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Micro‐MR angiography of normal and intratumoral vessels in mice using dedicated intravascular MR contrast agents with high generation of polyamidoamine dendrimer core: Reference to pharmacokinetic properties of dendrimer‐based MR contrast agents
Author(s) -
Kobayashi Hisataka,
Kawamoto Satomi,
Saga Tsuneo,
Sato Noriko,
Hiraga Akira,
Konishi Junji,
Togashi Kaori,
Brechbiel Martin W.
Publication year - 2001
Publication title -
journal of magnetic resonance imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.563
H-Index - 160
eISSN - 1522-2586
pISSN - 1053-1807
DOI - 10.1002/jmri.10025
Subject(s) - dendrimer , biodistribution , pharmacokinetics , magnetic resonance imaging , mri contrast agent , chemistry , gadolinium , contrast (vision) , kidney , nuclear medicine , medicine , radiology , pharmacology , in vitro , biochemistry , organic chemistry , artificial intelligence , computer science
Pharmacokinetic characteristics of intravascular macromolecular magnetic resonance imaging (MRI) contrast agents with polyamidoamine dendrimer cores smaller than generation‐7 were previously studied in the literature. To evaluate the effects of greater hepatic uptake on the pharmacokinetics of the larger generation dendrimers, the MRI contrast agents GxD‐(1B4M‐Gd) 2 x+2were synthesized with generation‐7, ‐8, and ‐9 polyamidoamine dendrimers and 2‐( p ‐isothiocyanatobenzyl)‐6‐methyl‐diethylenetriaminepentaacetic acid (1B4M). Their pharmacokinetic characteristics in mice were compared with that of G6D‐(1B4M‐Gd) 256 . In biodistribution and dynamic micro‐MRI studies, significantly less renal accumulation of G7D‐(1B4M‐Gd) 512 , G8D‐(1B4M‐Gd) 1024 , and G9D‐(1B4M‐Gd) 2048 was shown compared to G6D‐(1B4M‐Gd) 256 ( P < 0.01). There was a significantly greater accumulation of G8D‐(1B4M‐Gd) 1024 and G9D‐(1B4M‐Gd) 2048 in the liver compared to G6D‐(1B4M‐Gd) 256 and G7D‐(1B4M‐Gd) 512 ( P < 0.01). The highest blood retention of all dendrimer‐based MRI contrast agents was exhibited by G7D‐(1B4M‐Gd) 512 ( P < 0.01). The normal and intratumoral fine vessels of approximately 100 μm diameter were visualized in normal or tumor‐bearing mice by high resolution three‐dimensional‐micro‐MR angiographs with G7D‐(1B4M‐Gd) 512 and G8D‐(1B4M‐Gd) 1024 with good vessel‐to‐soft tissue contrast. In summary, increased accumulation in the liver with concomitant decreased uptake in the kidney was caused by increased molecular sizes of the dendrimer‐based MRI contrast agents. J. Magn. Reson. Imaging 2001;14:705–713. © 2001 Wiley‐Liss, Inc.